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Rat arterial smooth muscle devoid of ryanodine receptor function: effects on cellular Ca2+ handling

Dreja, Karl LU ; Nordström, Ina LU and Hellstrand, Per LU (2001) In British Journal of Pharmacology 132(8). p.1957-1966
Abstract
The roles of intracellular Ca2+ stores and ryanodine (Ry) receptors for vascular Ca2+ homeostasis and viability were investigated in rat tail arterial segments kept in organ culture with Ry (10 100 M) for up to 4 days. Acute exposure to Ry or the non-deactivating ryanodine analogue C10-Oeq glycyl ryanodine (10 M) eliminated Ca2+ release responses to caffeine (20 mM) and noradrenaline (NA, 10 M), whereas responses to NA, but not caffeine, gradually returned to normal within 4 days of exposure to Ry. Ry receptor protein was detected on Western blots in arteries cultured either with or without Ry. Brief Ca2+ release events (sparks) were absent after culture with Ry, whereas Ca2+ waves still occurred. The propagation velocity of waves was... (More)
The roles of intracellular Ca2+ stores and ryanodine (Ry) receptors for vascular Ca2+ homeostasis and viability were investigated in rat tail arterial segments kept in organ culture with Ry (10 100 M) for up to 4 days. Acute exposure to Ry or the non-deactivating ryanodine analogue C10-Oeq glycyl ryanodine (10 M) eliminated Ca2+ release responses to caffeine (20 mM) and noradrenaline (NA, 10 M), whereas responses to NA, but not caffeine, gradually returned to normal within 4 days of exposure to Ry. Ry receptor protein was detected on Western blots in arteries cultured either with or without Ry. Brief Ca2+ release events (sparks) were absent after culture with Ry, whereas Ca2+ waves still occurred. The propagation velocity of waves was equal (19 m s-1) in tissue cultured either with or without Ry. Inhibition of Ca2+ accumulation into the sarcoplasmic reticulum (SR) by culture with caffeine (5 mM), cyclopiazonic acid or thapsigargin (both 10 M) decreased contractility due to Ca2+-induced cell damage. In contrast, culture with Ry did not affect contractility. Removal of Ca2+ from the cytosol following a Ca2+ load was retarded after Ry culture. Thapsigargin reduced the rate of Ca2+ removal in control cultured rings, but had no effect after Ry culture. It is concluded that intracellular Ca2+ stores recover during chronic Ry treatment, while Ry receptors remain non-functional. Ry receptor activity is required for Ca2+ sparks and for SR-dependent recovery from a Ca2+ load, but not for Ca2+ waves or basal Ca2+ homeostasis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ryanodine receptors, smooth muscle, Ca2+ stores, sarcoplasmic reticulum, organ culture, Ca2+ sparks, Ca2+ waves
in
British Journal of Pharmacology
volume
132
issue
8
pages
1957 - 1966
publisher
The British Pharmacological Society
external identifiers
  • wos:000168326100038
  • scopus:0035041734
ISSN
1476-5381
DOI
10.1038/sj.bjp.0703986
language
English
LU publication?
yes
id
f575a5a8-dfd8-444e-b4d9-1276c8d9e5a6 (old id 131318)
date added to LUP
2007-07-11 13:24:48
date last changed
2018-01-07 09:15:38
@article{f575a5a8-dfd8-444e-b4d9-1276c8d9e5a6,
  abstract     = {The roles of intracellular Ca2+ stores and ryanodine (Ry) receptors for vascular Ca2+ homeostasis and viability were investigated in rat tail arterial segments kept in organ culture with Ry (10 100 M) for up to 4 days. Acute exposure to Ry or the non-deactivating ryanodine analogue C10-Oeq glycyl ryanodine (10 M) eliminated Ca2+ release responses to caffeine (20 mM) and noradrenaline (NA, 10 M), whereas responses to NA, but not caffeine, gradually returned to normal within 4 days of exposure to Ry. Ry receptor protein was detected on Western blots in arteries cultured either with or without Ry. Brief Ca2+ release events (sparks) were absent after culture with Ry, whereas Ca2+ waves still occurred. The propagation velocity of waves was equal (19 m s-1) in tissue cultured either with or without Ry. Inhibition of Ca2+ accumulation into the sarcoplasmic reticulum (SR) by culture with caffeine (5 mM), cyclopiazonic acid or thapsigargin (both 10 M) decreased contractility due to Ca2+-induced cell damage. In contrast, culture with Ry did not affect contractility. Removal of Ca2+ from the cytosol following a Ca2+ load was retarded after Ry culture. Thapsigargin reduced the rate of Ca2+ removal in control cultured rings, but had no effect after Ry culture. It is concluded that intracellular Ca2+ stores recover during chronic Ry treatment, while Ry receptors remain non-functional. Ry receptor activity is required for Ca2+ sparks and for SR-dependent recovery from a Ca2+ load, but not for Ca2+ waves or basal Ca2+ homeostasis.},
  author       = {Dreja, Karl and Nordström, Ina and Hellstrand, Per},
  issn         = {1476-5381},
  keyword      = {Ryanodine receptors,smooth muscle,Ca2+ stores,sarcoplasmic reticulum,organ culture,Ca2+ sparks,Ca2+ waves},
  language     = {eng},
  number       = {8},
  pages        = {1957--1966},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Rat arterial smooth muscle devoid of ryanodine receptor function: effects on cellular Ca2+ handling},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0703986},
  volume       = {132},
  year         = {2001},
}